[Construction of a Predictive Model for Diabetes Mellitus Type 2 in Middle-Aged and Elderly Populations Based on the Medical Checkup Data of National Basic Public Health Service]. / åŸºäºŽå›½å®¶åŸºæœ¬å ¬å ±å«ç”ŸæœåŠ¡ä½“æ£€çš„ä¸­è€å¹´äºº2åž‹ç³–å°¿ç— é£Žé™©é¢„æµ‹æ¨¡åž‹æž„å»º.

Objective: To establish a universally applicable logistic risk prediction model for diabetes mellitus type 2 (T2DM) in the middle-aged and elderly populations based on the results of a Meta-analysis, and to validate and confirm the efficacy of the model using the follow-up data of medical check-ups of National Basic Public Health Service. Methods: Cohort studies evaluating T2DM risks were identified in Chinese and English databases. The logistic model utilized Meta-combined effect values such as the odds ratio (OR) to derive ß, the partial regression coefficient, of the logistic model. The Meta-combined incidence rate of T2DM was used to obtain the parameter α of the logistic model. Validation of the predictive performance of the model was conducted with the follow-up data of medical checkups of National Basic Public Health Service. The follow-up data came from a community health center in Chengdu and were collected between 2017 and 2022 from 7602 individuals who did not have T2DM at their baseline medical checkups done at the community health center. This community health center was located in an urban-rural fringe area with a large population of middle-aged and elderly people. Results: A total of 40 cohort studies were included and 10 items covered in the medical checkups of National Basic Public Health Service were identified in the Meta-analysis as statistically significant risk factors for T2DM, including age, central obesity, smoking, physical inactivity, impaired fasting glucose, a reduced level of high-density lipoprotein cholesterol (HDL-C), hypertension, body mass index (BMI), triglyceride glucose (TYG) index, and a family history of diabetes, with the OR values and 95% confidence interval (CI) being 1.04 (1.03, 1.05), 1.55 (1.29, 1.88), 1.36 (1.11, 1.66), 1.26 (1.07, 1.49), 3.93 (2.94, 5.24), 1.14 (1.06, 1.23), 1.47 (1.34, 1.61), 1.11 (1.05, 1.18), 2.15 (1.75, 2.62), and 1.66 (1.55, 1.78), respectively, and the combined ß values being 0.039, 0.438, 0.307, 0.231, 1.369, 0.131, 0.385, 0.104, 0.765, and 0.507, respectively. A total of 37 studies reported the incidence rate, with the combined incidence being 0.08 (0.07, 0.09) and the parameter α being -2.442 for the logistic model. The logistic risk prediction model constructed based on Meta-analysis was externally validated with the data of 7602 individuals who had medical checkups and were followed up for at least once. External validation results showed that the predictive model had an area under curve (AUC) of 0.794 (0.771, 0.816), accuracy of 74.5%, sensitivity of 71.0%, and specificity of 74.7% in the 7602 individuals. Conclusion: The T2DM risk prediction model based on Meta-analysis has good predictive performance and can be used as a practical tool for T2DM risk prediction in middle-aged and elderly populations.

Computational determination of the S1(Ã1A″) absorption spectra of HONO and DONO using full-dimensional neural network potential energy surfaces.

The Ã1A″ ← X̃1A' absorption spectra of HONO and DONO were simulated by a full six-dimensional quantum mechanical method based on the newly constructed potential energy surfaces for the ground and excited electronic states, which were represented by the neural network method utilizing over 36 000 ab initio energy points calculated at the multireference configuration interaction level with Davidson correction. The absorption spectrum of HONO/DONO comprises a superposition of the spectra from two isomers, namely, trans- and cis-HONO/DONO, due to their coexistence in the ground X̃1A' state. Our calculated spectra of both HONO and DONO were found to be in fairly good agreement with the experiment, including the energy positions and widths of the peaks. The dominant progression was assigned to the N=O stretch mode (20n) associated with trans-HONO/DONO, which can be attributed to the promotion of an electron to the π* orbital of N=O. Specifically, the resonances with higher vibrational quanta were found to be in the domain of the Feshbach-type resonances. The assignments of the spectra and mode specificity therein are discussed.

Hydrogen Spillover Mechanism at the Metal-Metal Interface in Electrocatalytic Hydrogenation.

Hydrogen spillover in metal-supported catalysts can largely enhance electrocatalytic hydrogenation performance and reduce energy consumption. However, its fundamental mechanism, especially at the metal-metal interface, remains further explored, impeding relevant catalyst design. Here, we theoretically profile that a large free energy difference in hydrogen adsorption on two different metals (|ΔGH-metal(i) - ΔGH-metal(ii)|) induces a high kinetic barrier to hydrogen spillover between the metals. Minimizing the difference in their d-band centers (Δεd) should reduce |ΔGH-metal(i) - ΔGH-metal(ii)|, lowering the kinetic barrier to hydrogen spillover for improved electrocatalytic hydrogenation. We demonstrated this concept using copper-supported ruthenium-platinum alloys with the smallest Δεd, which delivered record high electrocatalytic nitrate hydrogenation performance, with ammonia production rate of 3.45±0.12 mmol h-1 cm-2 and Faraday efficiency of 99.8±0.2 %, at low energy consumption of 21.4 kWh kgamm-1. Using these catalysts, we further achieve continuous ammonia and formic acid production with a record high-profit space.

Sex hormones in COVID-19 severity: The quest for evidence and influence mechanisms.

Studies have reported variable effects of sex hormones on serious diseases. Severe disease and mortality rates in COVID-19 show marked gender differences that may be related to sex hormones. Sex hormones regulate the expression of the viral receptors ACE2 and TMPRSS2, which affect the extent of viral infection and consequently cause variable outcomes. In addition, sex hormones have complex regulatory mechanisms that affect the immune response to viruses. These hormones also affect metabolism, leading to visceral obesity and severe disease can result from complications such as thrombosis. This review presents the latest researches on the regulatory functions of hormones in viral receptors, immune responses, complications as well as their role in COVID-19 progression. It also discusses the therapeutic possibilities of these hormones by reviewing the recent findings of clinical and assay studies.

Biotransformation of chenodeoxycholic acid by human intestinal fungi and the agonistic effects on FXR.

Bile acids play a vital role in modulating host metabolism, with chenodeoxycholic acid (CDCA) standing out as a primary bile acid that naturally activates farnesoid X receptor (FXR). In this study, we investigated the microbial transformations of CDCA by seven human intestinal fungal species. Our findings revealed that hydroxylation and dehydrogenation were the most prevalent metabolic pathways. Incubation of CDCA with Rhizopus microspores (PT2906) afforded eight undescribed compounds (6-13) alongside five known analogs (1-5) which were elucidated by HRESI-MS and NMR data. Notably, compounds 8, 12 and 13 exhibited an inhibitory effect on FXR in contrast to the FXR activation observed with CDCA in vitro assays. This study shone a light on the diverse transformations of CDCA by intestinal fungi, unveiling potential modulators of FXR activity with implications for host metabolism.

Investigation into the characteristics of electron beam-aged microplastics and adsorption behavior of dibutyl phthalate.

Microplastics are increasingly prevalent in the environment, and their ability to adsorb various organic additives, posing harm to organisms, has attracted growing attention. Currently, there are no effective methods to age microplastics, and there is limited discussion on the subsequent treatment of aged microplastics. This study focuses on micro polyethylene (PE) and employs electron beam technology for aging treatment, investigating the adsorption and leaching behavior between PE and dibutyl phthalate (DBP) before and after aging. Experimental results indicate that with increasing doses of electron beam irradiation, the surface microstructure of PE worsens, inducing the generation of oxygen-containing functional groups on the surface of polyethylene. Comparative evaluations between electron beam aging and existing methods show that electron beam technology surpasses existing aging methods, achieving a level of aging exceeding 0.7 within an extremely short period of 1 min at doses exceeding 350 kGy. Adsorption experiments demonstrate that the adsorption between PE and DBP conforms to pseudo-second-order kinetics and the Freundlich model both before and after aging. The adsorption capacity of microplastics for DBP increases from 76.8 mg g-1 to 167.0 mg g-1 after treatment, exceeding that of conventional DBP adsorbents. Electron beam irradiation causes aging of microplastics mainly through the generation of ·OH, which lead to the formation of oxygen-containing functional groups on the microplastics' surface, thereby enhancing their adsorption capacity for DBP. This provides a new perspective for the degradation of aged microplastics and composite pollutants.

Hyperbaric Oxygen Boosts Antitumor Efficacy of Copper-Diethyldithiocarbamate Nanoparticles against Pancreatic Ductal Adenocarcinoma by Regulating Cancer Stem Cell Metabolism.

Cuproptosis-based cancer nanomedicine has received widespread attention recently. However, cuproptosis nanomedicine against pancreatic ductal adenocarcinoma (PDAC) is severely limited by cancer stem cells (CSCs), which reside in the hypoxic stroma and adopt glycolysis metabolism accordingly to resist cuproptosis-induced mitochondria damage. Here, we leverage hyperbaric oxygen (HBO) to regulate CSC metabolism by overcoming tumor hypoxia and to augment CSC elimination efficacy of polydopamine and hydroxyethyl starch stabilized copper-diethyldithiocarbamate nanoparticles (CuET@PH NPs). Mechanistically, while HBO and CuET@PH NPs inhibit glycolysis and oxidative phosphorylation, respectively, the combination of HBO and CuET@PH NPs potently suppresses energy metabolism of CSCs, thereby achieving robust tumor inhibition of PDAC and elongating mice survival importantly. This study reveals novel insights into the effects of cuproptosis nanomedicine on PDAC CSC metabolism and suggests that the combination of HBO with cuproptosis nanomedicine holds significant clinical translation potential for PDAC patients.

From virus to immune system: Harnessing membrane-derived vesicles to fight COVID-19 by interacting with biological molecules.

Emerging and re-emerging viral pandemics have emerged as a major public health concern. Highly pathogenic coronaviruses, which cause severe respiratory disease, threaten human health and socioeconomic development. Great efforts are being devoted to the development of safe and efficacious therapeutic agents and preventive vaccines to combat them. Nevertheless, the highly mutated virus poses a challenge to drug development and vaccine efficacy, and the use of common immunomodulatory agents lacks specificity. Benefiting from the burgeoning intersection of biological engineering and biotechnology, membrane-derived vesicles have shown superior potential as therapeutics due to their biocompatibility, design flexibility, remarkable bionics, and inherent interaction with phagocytes. The interactions between membrane-derived vesicles, viruses, and the immune system have emerged as a new and promising topic. This review provides insight into considerations for developing innovative antiviral strategies and vaccines against SARS-CoV-2. First, membrane-derived vesicles may provide potential biomimetic decoys with a high affinity for viruses to block virus-receptor interactions for early interruption of infection. Second, membrane-derived vesicles could help achieve a balanced interplay between the virus and the host's innate immunity. Finally, membrane-derived vesicles have revealed numerous possibilities for their employment as vaccines.

Research advances of tissue-derived extracellular vesicles in cancers.

BACKGROUND: Extracellular vesicles (EVs) can mediate cell-to-cell communication and affect various physiological and pathological processes in both parent and recipient cells. Currently, extensive research has focused on the EVs derived from cell cultures and various body fluids. However, insufficient attention has been paid to the EVs derived from tissues. Tissue EVs can reflect the microenvironment of the specific tissue and the cross-talk of communication among different cells, which can provide more accurate and comprehensive information for understanding the development and progression of diseases. METHODS: We review the state-of-the-art technologies involved in the isolation and purification of tissue EVs. Then, the latest research progress of tissue EVs in the mechanism of tumor occurrence and development is presented. And finally, the application of tissue EVs in the clinical diagnosis and treatment of cancer is anticipated. RESULTS: We evaluate the strengths and weaknesses of various tissue processing and EVs isolation methods, and subsequently analyze the significance of protein characterization in determining the purity of tissue EVs. Furthermore, we focus on outlining the importance of EVs derived from tumor and adipose tissues in tumorigenesis and development, as well as their potential applications in early tumor diagnosis, prognosis, and treatment. CONCLUSION: When isolating and characterizing tissue EVs, the most appropriate protocol needs to be specified based on the characteristics of different tissues. Tissue EVs are valuable in the diagnosis, prognosis, and treatment of tumors, and the potential risks associated with tissue EVs need to be considered as therapeutic agents.

Phenotypic and genetic effect of carotid intima-media thickness on the risk of stroke.

While carotid intima-media thickness (cIMT) as a noninvasive surrogate measure of atherosclerosis is widely considered a risk factor for stroke, the intrinsic link underlying cIMT and stroke has not been fully understood. We aimed to evaluate the clinical value of cIMT in stroke through the investigation of phenotypic and genetic relationships between cIMT and stroke. We evaluated phenotypic associations using observational data from UK Biobank (N = 21,526). We then investigated genetic relationships leveraging genomic data conducted in predominantly European ancestry for cIMT (N = 45,185) and any stroke (AS, Ncase/Ncontrol=40,585/406,111). Observational analyses suggested an increased hazard of stroke per one standard deviation increase in cIMT (cIMTmax-AS: hazard ratio (HR) = 1.39, 95%CI = 1.09-1.79; cIMTmean-AS: HR = 1.39, 95%CI = 1.09-1.78; cIMTmin-AS: HR = 1.32, 95%CI = 1.04-1.68). A positive global genetic correlation was observed (cIMTmax-AS: [Formula: see text]=0.23, P=9.44 × 10-5; cIMTmean-AS: [Formula: see text]=0.21, P=3.00 × 10-4; cIMTmin-AS: [Formula: see text]=0.16, P=6.30 × 10-3). This was further substantiated by five shared independent loci and 15 shared expression-trait associations. Mendelian randomization analyses suggested no causal effect of cIMT on stroke (cIMTmax-AS: odds ratio (OR)=1.12, 95%CI=0.97-1.28; cIMTmean-AS: OR=1.09, 95%CI=0.93-1.26; cIMTmin-AS: OR=1.03, 95%CI = 0.90-1.17). A putative association was observed for genetically predicted stroke on cIMT (AS-cIMTmax: beta=0.07, 95%CI = 0.01-0.13; AS-cIMTmean: beta=0.08, 95%CI = 0.01-0.15; AS-cIMTmin: beta = 0.08, 95%CI = 0.01-0.16) in the reverse direction MR, which attenuated to non-significant in sensitivity analysis. Our work does not find evidence supporting causal associations between cIMT and stroke. The pronounced cIMT-stroke association is intrinsic, and mostly attributed to shared genetic components. The clinical value of cIMT as a surrogate marker for stroke risk in the general population is likely limited.

High-Performance Thin-Layer Chromatography Coupled with Single Quadrupole: Application the Identification and Differentiation of Rehmanniae Radix and Its Different Processing Products from Raw Materials to Commercial Products.

The authentication of ingredients in formulas is crucial yet challenging, particularly for constituents with comparable compositions but vastly divergent efficacy. Rehmanniae Radix and its derivatives are extensively utilized in food supplements, which contain analogous compositions but very distinct effects. Rehmanniae Radix, also a difficult-to-detect herbal ingredient, was chosen as a case to explore a novel HPTLC-QDa MS technique for the identification of herbal ingredients in commercial products. Through systematic condition optimization, including thin layer and mass spectrometry, a stable and reproducible HPTLC-QDa MS method was established, which can simultaneously detect oligosaccharides and iridoids. Rehmannia Radix and its processed products were then analyzed to screen five markers that could distinguish between raw and prepared Rehmannia Radix. An HPTLC-QDa-SIM method was further established for formula detection by using the five markers and validated using homemade prescriptions and negative controls. Finally, this method was applied to detect raw and prepared Rehmannia Radix in 12 commercial functional products and supplements.

A prospective cohort study of exposure to household pesticide with cardiovascular diseases mortality in older adults.

OBJECTIVES: We examined the associations of self-reported exposures, and urinary metabolites related to household pesticide with cardiovascular disease (CVD) mortality in older adults based on the 2007 to 2014 waves of National Health and Nutrition Examination Survey (NHANES). METHODS: Information on application and urinary metabolites related to household pesticide exposure were collected. We estimated the risks of household pesticide exposure, urinary metabolites with subsequent incident CVD death using Cox proportional hazards regression models. The indirect effects of urinary metabolites and effect modifications were examined. RESULTS: The participants who reported exposure to household pesticide had a higher risk of incident CVD death (adjusted HR 1.40, 95% CI 1.08 to 1.81). Per 1-log10 increase in urinary N, N-diethyl-3-methylbenzamide (DEET) related to household insect repellents was associated with a higher risk of incident CVD death (adjusted HR 1.97, 95% CI 1.14 to 3.40). Urinary DEET explained 4.21% of the total association between household pesticide exposure and CVD death risk. The participants who persisted a low level of health diet exhibited pronounced CVD death risks with household pesticide exposures. CONCLUSIONS: Exposure to household pesticide, especially household insect repellents, was consistently associated with an elevated CVD death risk in older adults. A heatlhy diet could partly attenuate the associations.

The effects of Nardosinone on levodopa intervention in the treatment of Parkinson's disease.

BACKGROUND: The roots and rhizomes of Nardostachys jatamansi DC. are reported to be useful for the treatment of Parkinson's disease (PD). Previous research has also shown that Nardosinone, the main active component isolated from Nardostachys jatamansi DC., exhibits the potential to treat PD. AIM OF THE STUDY: To investigate how the effects of Nardosinone could assist levodopa in the treatment of PD, how this process changes the intestinal flora, and to explore the effective forms of Nardosinone in the intestinal flora. MATERIAL AND METHODS: We used behavioral experiments, and hematoxylin-eosin staining and immunohistochemical staining, to investigate the effects of a combination of Nardosinone and levodopa on rotenone-induced PD rats. In addition, we used LC/MS-MS to determine the levels of levodopa, 5-hydroxytryptamine, dopamine and its metabolite 3, 4-dihydroxyphenylacetic acid, and homovanillic acid, to investigate the effect of the intestinal flora on co-administration in the treatment of PD. LC/MS-MS was also used to detect the metabolites of Nardosinone on the gastrointestinal tract and intestinal flora. RESULTS: The behavioral disorders and neuronal damage associated with PD were significantly improved following the co-administration. Analysis also revealed that the co-administration increased the levels of five neurotransmitters in the striatum, plasma and feces. In vitro experiments further demonstrated that the levels of dopamine and levodopa were increased in the intestinal flora. In total, five metabolites of Nardosinone were identified. CONCLUSION: Our findings indicate that Nardosinone and its metabolites might act as a potential adjutant to enhance the efficacy of levodopa via the intestinal flora, thus expanding the therapeutic potential of the combination of Chinese and Western medicine as a treatment method for PD.

Hydrogen Spillover Phenomenon at the Interface of Metal-Supported Electrocatalysts for Hydrogen Evolution.

ConspectusHydrogen spillover, as a well-known phenomenon for thermal hydrogenation, generally involves the migration of active hydrogen on the surface of metal-supported catalysts. For thermocatalytic hydrogenation, hydrogen spillover generally takes place from metals with superiority for dissociating hydrogen molecules to supports with strong hydrogen adsorption under a H2 environment with high pressures. The former can bring high hydrogen chemical potential to largely reduce the kinetic barrier of the migration of active hydrogen species from metals to supports. At the same time, the latter can make H* migration thermodynamically spontaneous. For these reasons, hydrogen spillover is a common interfacial phenomenon occurring on metal-supported catalysts during thermocatalysis. Recently, this phenomenon has been observed for the exceptionally enhanced electrocatalytic performance for hydrogen evolution and other electrocatalytic organic synthesis. Different from hydrogen spillover for thermocatalysis under high H2 pressure, hydrogen spillover for electrocatalysis involves the migration of active hydrogen species (H*) from metals with strong hydrogen adsorption to supports with weak hydrogen adsorption, thereby suffering from a thermodynamically unfavorable process accompanied by a high kinetic barrier. Thus, the occurrence of hydrogen spillover at the electrocatalytic interface is not easy, and successful cases are rare. Understanding the underlying nature of hydrogen spillover at the electrocatalytic interface of metal-supported catalysts is critical to the rational design of advanced electrocatalysts.In this Account, we provide in-depth insights into recent advances in hydrogen spillover at the electrocatalytic interface for a significantly enhanced hydrogen evolution performance. Electron accumulation at the metal-support interface induces severe interfacial H* trapping and is recognized as the main factor in the failed hydrogen spillover. Given this, we developed two novel strategies to promote the occurrence of hydrogen spillover at the electrocatalytic interface. These strategies include (i) the introduction of ligand environments to enrich the local hydrogen coverage on metals and lower the barrier for interfacial hydrogen spillover and (ii) the minimization of work function difference between metals and supports (ΔΦ) to relieve electron accumulation and lower the kinetic barrier for hydrogen spillover. Also, we summarize the previously reported strategy of shortening the metal-support interface distance to lower the kinetic barrier for interfacial hydrogen spillover. Afterward, some criteria and methodologies are proposed to identify the hydrogen spillover phenomenon at the electrocatalytic interface. Finally, the remaining challenges and future perspectives are also discussed. Based on this Account, we aim to provide new insights into electrocatalysis, particularly the targeted control of hydrogen spillover at the electrocatalytic interface, and then to offer guidelines for the rational design of advanced electrocatalysts.

Risk factors for prostate cancer: An umbrella review of prospective observational studies and mendelian randomization analyses.

BACKGROUND: The incidence of prostate cancer is increasing in older males globally. Age, ethnicity, and family history are identified as the well-known risk factors for prostate cancer, but few modifiable factors have been firmly established. The objective of this study was to identify and evaluate various factors modifying the risk of prostate cancer reported in meta-analyses of prospective observational studies and mendelian randomization (MR) analyses. METHODS AND FINDINGS: We searched PubMed, Embase, and Web of Science from the inception to January 10, 2022, updated on September 9, 2023, to identify meta-analyses and MR studies on prostate cancer. Eligibility criteria for meta-analyses were (1) meta-analyses including prospective observational studies or studies that declared outcome-free at baseline; (2) evaluating the factors of any category associated with prostate cancer incidence; and (3) providing effect estimates for further data synthesis. Similar criteria were applied to MR studies. Meta-analysis was repeated using the random-effects inverse-variance model with DerSimonian-Laird method. Quality assessment was then conducted for included meta-analyses using AMSTAR-2 tool and for MR studies using STROBE-MR and assumption evaluation. Subsequent evidence grading criteria for significant associations in meta-analyses contained sample size, P values and 95% confidence intervals, 95% prediction intervals, heterogeneity, and publication bias, assigning 4 evidence grades (convincing, highly suggestive, suggestive, or weak). Significant associations in MR studies were graded as robust, probable, suggestive, or insufficient considering P values and concordance of effect directions. Finally, 92 selected from 411 meta-analyses and 64 selected from 118 MR studies were included after excluding the overlapping and outdated studies which were published earlier and contained fewer participants or fewer instrument variables for the same exposure. In total, 123 observational associations (45 significant and 78 null) and 145 causal associations (55 significant and 90 null) were categorized into lifestyle; diet and nutrition; anthropometric indices; biomarkers; clinical variables, diseases, and treatments; and environmental factors. Concerning evidence grading on significant associations, there were 5 highly suggestive, 36 suggestive, and 4 weak associations in meta-analyses, and 10 robust, 24 probable, 4 suggestive, and 17 insufficient causal associations in MR studies. Twenty-six overlapping factors between meta-analyses and MR studies were identified, with consistent significant effects found for physical activity (PA) (occupational PA in meta: OR = 0.87, 95% CI: 0.80, 0.94; accelerator-measured PA in MR: OR = 0.49, 95% CI: 0.33, 0.72), height (meta: OR = 1.09, 95% CI: 1.06, 1.12; MR: OR = 1.07, 95% CI: 1.01, 1.15, for aggressive prostate cancer), and smoking (current smoking in meta: OR = 0.74, 95% CI: 0.68, 0.80; smoking initiation in MR: OR = 0.91, 95% CI: 0.86, 0.97). Methodological limitation is that the evidence grading criteria could be expanded by considering more indices. CONCLUSIONS: In this large-scale study, we summarized the associations of various factors with prostate cancer risk and provided comparisons between observational associations by meta-analysis and genetically estimated causality by MR analyses. In the absence of convincing overlapping evidence based on the existing literature, no robust associations were identified, but some effects were observed for height, physical activity, and smoking.

Comprehensive HRMS Screening and Risk Assessments of Aristolochic Acid Analogues in Asari Radix et Rhizoma and Related Commercial Health Products.

Aristolochic acid analogues (AAAs) are well-known toxins. We performed the first comprehensive screening on AAAs in Asari Radix et Rhizoma (underground part of Asarum heterotropoides Schmidt), the only Aristolochiaceae plant widely used in clinical practice. LC-HRMS revealed 70 trace AAAs using polygonal mass defect filtering and precursor ion list strategies, 38 of which were newly discovered in A. heterotropoides. UHPLC-QTrap-MS/MS was then utilized for quantitative/semiquantitative analysis of 26 abundant compounds. Seventeen AAAs were detected from 91 batches of A. heterotropoides and 20 AAAs from 166 consumable products. For 141 Asari-containing proprietary products, aristolactam I and aristolactam II-glucoside exhibited the widest distribution, present in 98% products. AA IVa was the most abundant, detected in 91%. Notably, 60% of the products contained AA I (0.03-0.79 ppm). The safety was assessed using linear extrapolation, permitted daily exposure, cumulative amount, and the margin of exposure. It is recommended that AA I content be limited to 3 ppm.

miR-29a-KLF4 signaling inhibits breast tumor initiation by regulating cancer stem cells.

Cancer stem cells (CSCs) are known for their potent ability to drive tumor initiation and recurrence, yet the molecular mechanisms regulating CSCs are still unclear. Our study found a positive correlation between increased levels of miR-29a and better survival rates in early-stage breast cancer patients, but a negative correlation in late-stage patients, suggesting a dual function of miR-29a in regulating breast cancer. Furthermore, miR-29a showed significant downregulation in the ALDH+ breast cancer stem cell population compared to non-stem cancer cells. Overexpression of miR-29a in human breast cancer cells reduced the proportion of CSCs, suppressed their ability to form mammospheres, and inhibited the expression of stemness genes SOX2, KLF4, and hTERT in vitro. Conversely, knockdown of miR-29a in breast cancer cells showed opposite effects. Tumor xenograft experiments revealed that miR-29a overexpression significantly inhibited tumorigenesis initiated by MDA-MB-231 cell transplantation in nude mice. We further demonstrated that Krüppel-like factor 4 (KLF4), a key gene that regulates cell stemness, was a direct target of miR-29a in breast cancer cells. miR-29a suppressed the expression of KLF4 at both mRNA and protein levels. Reintroduction of KLF4 into breast cancer cells rescued the miR-29a-induced CSC suppression phenotype. In summary, our study is the first to demonstrate that miR-29a-KLF4 signaling inhibits breast tumor initiation by regulating CSCs, which provides novel therapeutic targets for preventing breast tumor initiation.

Tandem Electrocatalytic Alkyne Semihydrogenation over Bicomponent Catalysts through Hydrogen Spillover.

Electrocatalytic alkyne semihydrogenation under mild conditions is a more attractive approach for alkene production than industrial routes but suffers from either low production efficiency or high energy consumption. Here, we describe a tandem catalytic concept that overcomes these challenges. Component (i), which can trap hydrogen effectively, is partnered with component (ii), which can readily release hydrogen for hydrogenation, to enable efficient generation of active hydrogen on component (i) at low overpotentials and timely (i)-to-(ii) hydrogen spillover and facile desorptive hydrogenation on component (ii). We examine this concept over bicomponent palladium-copper catalysts for the production of representative 2-methyl-3-butene-2-ol (MBE) from 2-methyl-3-butyne-2-ol (MBY) and achieve a record high MBE production rate of 1.44 mmol h-1 cm-2 and a Faraday efficiency of ~88.8 % at a low energy consumption of 1.26 kWh kgMBE -1. With these catalysts, we further achieve 60 h continuous production of MBE with record high profit space.

Integration of machine learning for developing a prognostic signature related to programmed cell death in colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) presents a significant global health burden, characterized by a heterogeneous molecular landscape and various genetic and epigenetic alterations. Programmed cell death (PCD) plays a critical role in CRC, offering potential targets for therapy by regulating cell elimination processes that can suppress tumor growth or trigger cancer cell resistance. Understanding the complex interplay between PCD mechanisms and CRC pathogenesis is crucial. This study aims to construct a PCD-related prognostic signature in CRC using machine learning integration, enhancing the precision of CRC prognosis prediction. METHOD: We retrieved expression data and clinical information from the Cancer Genome Atlas and Gene Expression Omnibus (GEO) datasets. Fifteen forms of PCD were identified, and corresponding gene sets were compiled. Machine learning algorithms, including Lasso, Ridge, Enet, StepCox, survivalSVM, CoxBoost, SuperPC, plsRcox, random survival forest (RSF), and gradient boosting machine, were integrated for model construction. The models were validated using six GEO datasets, and the programmed cell death score (PCDS) was established. Further, the model's effectiveness was compared with 109 transcriptome-based CRC prognostic models. RESULT: Our integrated model successfully identified differentially expressed PCD-related genes and stratified CRC samples into four subtypes with distinct prognostic implications. The optimal combination of machine learning models, RSF + Ridge, showed superior performance compared with traditional methods. The PCDS effectively stratified patients into high-risk and low-risk groups, with significant survival differences. Further analysis revealed the prognostic relevance of immune cell types and pathways associated with CRC subtypes. The model also identified hub genes and drug sensitivities relevant to CRC prognosis. CONCLUSION: The current study highlights the potential of integrating machine learning models to enhance the prediction of CRC prognosis. The developed prognostic signature, which is related to PCD, holds promise for personalized and effective therapeutic interventions in CRC.

Social support and cognitive activity and their associations with incident cognitive impairment in cognitively normal older adults.

OBJECTIVES: To explore the associations of social support, and cognitive activity with cognitive impairment incidence, and further examine the mediation effect of cognitive activity on the association between social support and cognitive impairment incidence based on a nationwide elderly Chinese cohort. METHODS: We collected the participants from an ongoing cohort of the Chinese Longitudinal Healthy Longevity Survey (CLHLS). A total of 9394 older adults aged 65 or more years and free of cognitive impairment who participated in the CLHLS between 2008 and 2018 were included. The information on social support and cognitive activity was collected through a questionnaire. The incident cognitive impairment cases were identified through the Mini-Mental State Examination scale (MMSE). Cox proportional hazard regression models were conducted to calculate the hazard ratios (HRs) and 95% confidence interval (CI) of social support and cognitive activity associated with cognitive impairment. We used casual mediation models to assess the indirect association of cognitive activities underlying the association between social support and cognitive impairment. RESULTS: The adjusted HRs (95% CI) of incident cognitive impairment were 0.956 (0.932 to 0.980), and 0.895 (0.859 to 0.933) associated with per 1 score increase in social support and cognitive activity score, respectively. Better adherence to social support was associated with a higher cognitive activity score (adjusted ß = 0.046, 95% CI[0.032-0.060]). The baseline cognitive activity, as well as the mean cognitive activity at baseline and during the first follow-up wave, mediate the association between social support and the incidence of cognitive impairment, accounting for 11.4% and 12.6% of the total association, respectively. The participants who were aged 80 years or older, or those with mild daily functional limitations gained more benefits in the development of cognitive activity related to social support, leading to a reduction in the risks of cognitive impairment. CONCLUSION: The results of this nationwide cohort provide consistent evidence linking social support, and cognitive activity to reduced risk of subsequent cognitive impairment incidence. These findings provide additional evidence to inform the social strategies to prevent cognitive impairment incidence in elderly people.